In recent years, the role of miRNAs in post-transcriptional gene regulation has come to the fore with strong evidence to indicate an important role for microRNAs (miRNAs) in the regulation of a wide range of fundamental biological processes. Notably, this includes the regulation of both endogenous tissue repair mechanisms and the growth and differentiation of stem cells (both adult and pluripotent). As a result, manipulation of miRNA signaling holds great promise for regenerative medicine, which aims to harness either endogenous or implanted cells to promote tissue repair. However, to fully realize this potential, it will be necessary to combine advances in our biological understanding with new technologies that allow precise spatiotemporal modulation of specific miRNA candidates. In this review, we highlight the role of miRNAs in tissue regeneration, discuss key challenges in translating this knowledge to the clinic, and outline recent technological advances that aim to address these issues. By combining a comprehensive knowledge of miRNA biology with cutting-edge delivery technologies, it is clear that miRNAs hold significant promise for tissue regenerative therapies in the future.